Abstract
In a model of male sterility (MTp53) owing to enforced p53 expression in spermatocytes II and spermatids of transgenic mice, we focused on the role of caspases. Most of them are expressed in all differentiation stages, but only the transcriptional levels of caspase-2 and caspase-3 are modified in MTp53 germ cells. In normal testis, cleaved caspase-3 and caspase-9 are detected during the elongation of spermatids. Despite this constitutive presence of caspases during terminal differentiation, calpains are the main effectors of germ cell loss in MTp53 testes: calpain 1 RNA levels are increased, caspase-3-like activity is markedly decreased while calpain activity is higher and the calpain inhibitor E64d ((2S, 3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester) reduces TUNEL labeling in MTp53 testis, whereas pancaspase inhibitor zVADfmk (N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone) has no effect. Our work suggests that despite the presence, and potent involvement, of caspases in male haploid cell maturation, calpains are the executioners of the death of terminally differentiating germ cells.
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Abbreviations
- MTI:
-
metallothionein
- SP:
-
side population
- CARD:
-
caspase recruitment domain
- zVADfmk:
-
N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone
- E64d:
-
(2S, 3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester
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Acknowledgements
This work was supported by the Association pour la Recherche contre le Cancer (Grant No. 5796) and by Electricité De France. We thank Patrick Flament for his precious help in maintaining our transgenic strains. We specially thank S Chevillard, V Joulin, B Lassalle and L Riou for their support and helpful discussions on this work. We thank D Marsh for his useful critical review of this manuscript.
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Coureuil, M., Fouchet, P., Prat, M. et al. Caspase-independent death of meiotic and postmeiotic cells overexpressing p53: calpain involvement. Cell Death Differ 13, 1927–1937 (2006). https://doi.org/10.1038/sj.cdd.4401887
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DOI: https://doi.org/10.1038/sj.cdd.4401887
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